Request for Funding

Medical Student Research Fellowship for Summer 2004

Mentor: Thomas M. Wilkie
Department: Pharmacology
Room number: K5.246
Mail Code: 9041
Phone number: 214-648-8581
E-mail: Thomas.Wilkie@utsouthwestern.edu
Project title: microRNA control of RGS gene expression

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

basic research

Brief Description of Project:

MicroRNAs are recently discovered regulators of mRNA stability and protein translation in vertebrates. MicroRNAs often target the 3' untranslated region (UTR) of mRNA to exert their regulatory control. These regulatory mechanisms appear to be conserved during 400 million years of vertebrate evolution, indicating strong selection pressure maintained these apparently important post-transcriptional mechanisms for regulating gene expression. In the proposed research project, we will study microRNA control of G protein signaling during the maintenance of energy homeostasis in liver. G protein signaling is used in all cells of metazoan organisms to coordinate intracellular responses to hormonal cues from neighboring cells or distant organs. G proteins are activated by hormones and feedback inhibited by Regulators of G protein Signaling (RGS) proteins. We identified microRNAs that target the G proteins and RGS proteins we study. We will characterize the function of these microRNAs, and the signaling pathways that regulate microRNA activity, using cell culture and recombinant DNA technology.

Previous Research Activities or Publications with Medical Students:

David Berman (MSTP)
Berman DM, Wilkie TM & Gilman AG (1996) GAIP and RGS4 are GTPase accelerating proteins (GAPs) for the Gi family of heterotrimeric guanine nucleotide binding proteins. Cell 86: 445-452.
Xu X, Zeng W, Popov S, Berman DM, Davignon I, Yu K, Yowe D, Offermanns S, Muallem S & Wilkie TM (1999) RGS4 determines signaling specificity of Gq-coupled receptors. J Biol Chem 274: 3549-3556.

Kim Sweet (Medical Student)
Davignon I, Barnard M, Gavrilova O, Sweet K & Wilkie TM (1996) Gene structure of murine Gna11 and Gna15: Tandemly duplicated Gq class G protein alpha subunit genes.
Genomics 31: 359-366.

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